Redox-Active Microneedle Platforms for ROS Modulation in Chronic Wound Healing

Abstract

Chronic wounds represent a growing clinical and economic burden, and their impaired healing is closely linked to a disrupted redox environment. Reactive oxygen species (ROS) are essential signaling molecules that regulate each phase of wound healing, from hemostasis and inflammation through proliferation and remodeling. ROS at physiological levels regulate antimicrobial defense, angiogenesis and cellular migration. However, the persistent oxidative overload that characterizes chronic wounds sustains inflammation and delays tissue repair. Therefore, restoring redox balance instead of eliminating ROS has emerged as a rational therapeutic strategy. Microneedle (MN) platforms, particularly hydrogel-forming MNs , offer a uniquedelivery approach for this purpose by combining minimally invasive breach of the wound barrier with tunable swelling, high loading capacity, and controlled, localized release of redox-active agents into the wound bed and interstitial fluid. This review examines redox-active MN platforms for ROS modulation in chronic wound management, surveying ROS biology and wound healing physiology, the principal MN geometries and fabrication routes, and three major therapeutic categories: ROS-scavenging systems, ROS-generating systems and material and mechanistic design strategies beyond functional classification. We further discuss current challenges and future directions for translating these platforms toward clinical application. By integrating redox chemistry with MN engineering, hydrogel MN systems provide a versatile route to reestablish redox homeostasis and accelerate healing in chronic wounds. However, redox-active microneedle systems have not yet undergone clinical evaluation. Most efficacy data are derived from experimental animal wound models that do not accurately replicate the complexity of chronic wounds in humans, indicating that clinical translation remains at an early stage.